Development of the next-generation GPU-based Monte Carlo simulation platform for radiation-induced DNA damage calculations

项目摘要 电离辐射（IR）是现代医学的重要组成部分。当红外线穿透生物体时， 主要通过电离和激发将能量释放给介质。IR的能量偏离为： 媒介成分依赖，因此它被用来“看到”人类的内部结构， 红外在乳腺X线摄影、胸部X线、计算机断层扫描、正电子 红外线还可以损害生物体的结构和/或影响生物体的功能， 它以放射外科和放射疗法的形式用于治疗癌症。同时，IR也具有遗传毒性 和致癌性，呼吁人们不断努力了解其基本影响。 先进的细胞放射生物学研究表明，脱氧核糖核酸（DNA）的损伤在放射损伤中起着关键的作用。 对确定暴露于IR后的最终生物学甚至临床结果的作用。 假设当IR与DNA相互作用时，它可以在皮秒内通过初级和次级辐射破坏DNA， 二次红外线粒子和微秒由随后产生的辐射自由基。因此，必须 了解在各种辐射条件下，IR如何产生这种初始损伤。微观蒙特卡罗 (MC)像Geant 4-DNA这样能够计算这种破坏过程的模拟， 在定量假设检验中的重要作用。然而，在最先进的MC中存在几个问题 工具，使其难以满足日益增长的需求，先进的应用程序。其中包括低 处理“多体”问题的效率，最终计算结果的不确定性较大， 缺乏对整个细胞周期的支持以及有限访问/用户不友好的设计等。 在这个项目中，我们提出了解决上述问题，通过开发下一代MC仿真工具的IR 通过图形处理单元（GPU）的新实现诱导DNA损伤计算 并行计算，基于分子动力学/第一性原理的计算，新的DNA模型的发展 基于挤出模型和聚合物物理学，并且具有用户友好界面的开源版本。 一旦成功，开发的系统预计将作为下一代仿真平台， 计算由IR引起的初始DNA损伤，这可以成为成功的第一步。 完成了整个放射生物学过程的“自下而上”的多尺度模拟， 对放射医学有重大影响。

Project Summary Ionizing radiation (IR) is a critical component of modern medicine. When IR penetrates through the organism, it could depart its energy to the medium mainly through ionization and excitation. The energy departure of IR is medium composition dependent, and hence it is used to ‘see’ the inner structure of the human beings, enabling the application of IR in the medical imaging of mammography, chest x-rays, computational tomography, positron emission tomography, etc. IR can also damage the structure and/or affect the function of the organism and hence it is applied to treat cancer in the form of radiosurgery and radiotherapy. Meanwhile, IR is found to be genotoxic and carcinogenic, calling the non-ending effort to understand the fundamental effects. Advanced cellular radiobiological study exhibited that the damage of deoxyribonucleic acid (DNA) plays a pivotal role towards the determination of the final biological or even clinical outcome after exposure to IR. It is hypothesized that when IR interacts with DNA, it could damage DNA in picoseconds by the primary and secondary IR particles and in microseconds by subsequently generated radiation radicals. It is then essential to understand how IR produces this initial damage under various radiation conditions. Microscopic Monte Carlo (MC) simulation such as Geant4-DNA, capable of computing this damaging process, has been playing an important role in the quantitative hypothesis-test. However, there are several issues in the state-of-the-art MC tools, making it hard to meet the increasing demanding for advanced applications. These include the low efficiency in dealing with the ‘many-body’ problem, the relatively large uncertainty in the final computing results, the lack of support for the entire cell cycle and the limited-access/user-unfriendly designs, etc. In this project, we propose to solve the above issues by developing a next-generation MC simulation tool for IR induced DNA damage computation through the novel implementations of graphical processing units (GPUs) parallel computing, the molecular dynamics/first principles based computation, the new DNA model development based on the extrusion model and polymer physics, and the open-source release with user-friendly interface. Upon success, the developed system is expected to serve as a next-generation simulation platform for the calculation of the initial DNA damage caused by IR, which can become a profound first-step towards a successful accomplishment of the “bottom-up” multi-scale modeling for the entire radiobiological process, making a significant impact in radiation medicine.